title: Detection of a homozygous four base pair deletion in the protein X gene in a case of pyruvate dehydrogenase complex deficiency.
abstract: While the presence of a lipoyl-containing protein (protein X) separate from lipoyl transacetylase in the pyruvate dehydrogenase complex (PDC) has been known for some time, until recently only the cDNA for the yeast enzyme has been cloned. We have cloned, sequenced and characterized the cDNA encoding the human protein X and localized the protein X gene to chromosome 11p13. We also report here a new case of protein X deficiency identified immunologically, with decreased activity of PDC and without mutations in the E1alpha subunit or E1beta subunit. We report that the cDNA and gene of this patient for protein X has a homozygous 4 bp deletion, specifically in the putative mitochondrial targeting signal sequence which results in a premature stop codon. This is the first documented case of a molecular defect in pyruvate dehydrogenase protein X.
authors.affiliation: Department of Paediatrics, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Ling
authors.forename: G
authors.initials: G
authors.lastname: McEachern
authors.forename: A
authors.initials: A
authors.lastname: Seyda
authors.forename: N
authors.initials: N
authors.lastname: MacKay
authors.forename: S W
authors.initials: SW
authors.lastname: Scherer
authors.forename: S
authors.initials: S
authors.lastname: Bratinova
authors.forename: B
authors.initials: B
authors.lastname: Beatty
authors.forename: M L
authors.initials: ML
authors.lastname: Giovannucci-Uzielli
authors.forename: B H
authors.initials: BH
authors.lastname: Robinson
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D018388:Codon, Terminator; D006720:Homozygote; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics*; D011768:Pyruvate Dehydrogenase Complex / Q000096:biosynthesis / Q000138:chemical synthesis / Q000235:genetics*; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid
chemical_list: D018388:Codon, Terminator; D046911:Macromolecular Substances; C045867:PDHX protein, human; D010455:Peptides; D011768:Pyruvate Dehydrogenase Complex; D011994:Recombinant Proteins